The three-dimensional crystal structure of cholera toxin.
The three-dimensional crystal structure of cholera toxin.
复制标题
DOI：
10.1006/jmbi.1995.0456
复制
发表时间：
1995-08
影响因子：
5.6
通讯作者：
Rong-guang Zhang;D. Scott;M. Westbrook;S. Nance;B. Spangler;G. Shipley;E. Westbrook
中科院分区：
文献类型：
--
作者：
Rong-guang Zhang;D. Scott;M. Westbrook;S. Nance;B. Spangler;G. Shipley;E. Westbrook
霍乱的临床表现主要归因于分泌的六聚体AB 5肠毒素（霍乱原）的作用。我们已经独立地解决和完善的三维结构的choleragen在2.5 A的分辨率。晶体毒素的结构与大肠杆菌（LT）的不耐热肠毒素的结构非常相似，两者具有80%的序列同源性。在这两种情况下，楔形A亚基被束缚A2链松散地保持在五聚体B亚基平面上方。两种毒素之间最显著的差异发生在A2链的羧基末端。然而，LT的A2链的最后14个残基穿过B5组装体的中心孔形成具有末端环的延伸链，霍乱原的A2链在其整个长度上保持几乎连续的α-螺旋。A2链的四个羧基末端残基（KDEL序列），在LT的晶体结构中是无序的，在choleragen的电子密度图中清晰可见。在随附的文章中，我们描述了霍乱毒素（类霍乱毒素）的分离的B五聚体的三维结构。比较choleragen，choleragenoid和LT的晶体坐标为进一步的实验研究提供了坚实的三维基础。这些结构，沿着来自志贺氏菌和百日咳杆菌的相关毒素的结构，为合理设计新疫苗和抗微生物剂迈出了第一步。
The clinical manifestations of cholera are largely attributable to the actions of a secreted hexameric AB5 enterotoxin (choleragen). We have independently solved and refined the three-dimensional structure of choleragen at 2.5 A resolution. The structure of the crystalline toxin closely resembles that described for the heat-labile enterotoxin from Escherichia coli (LT) with which it shares 80% sequence homology. In both cases, the wedge-shaped A subunit is loosely held high above the plane of the pentameric B subunits by the tethering A2 chain. The most striking difference between the two toxins occurs at the carboxyl terminus of the A2 chain. Whereas the last 14 residues of the A2 chain of LT threading through the central pore of the B5 assembly form an extended chain with a terminal loop, the A2 chain of choleragen remains a nearly continuous alpha-helix throughout its length. The four carboxyl-terminal residues of the A2 chain (KDEL sequence), disordered in the crystal structure of LT, are clearly visible in choleragen's electron-density map. In the accompanying article we describe the three-dimensional structure of the isolated B pentamer of cholera toxin (choleragenoid). Comparison of the crystalline coordinates of choleragen, choleragenoid, and LT provides a solid three-dimensional foundation for further experimental investigation. These structures, along with those of related toxins from Shigella dysenteria and Bordetella pertussis, offer a first step towards the rational design of new vaccines and anti-microbial agents.